Our objectives are to determine the potential of Aflatoxin B1 (AFB1)-induced carcinogenesis in the respiratory system. Although humans and animals are exposed to AFB1 primarily via the diet, evidence indicates that AFB1 present in respirable particles (eg., grain dusts, cotton dusts), may be activated by pulmonary mixed function oxidases (MFOs), and hence may pose an occupational hazard to those exposed. Studies will be performed to characterize the metabolism of 14C-AFB1 in isolated, perfused tracheal and lung tissue, and in cultures of non-ciliated pulmonary bronchiolar (Clara) cells. Metabolites and water-soluble conjugates of AFB1 will be separated, identified, and quantitated by reverse-phase HPLC. Toxicokinetic studies will also be performed to characterize absorption, distribution, and elimination of 14C-AFB1 administered intratracheally in rats, mice, and rhesus monkeys. These in vivo and in vitro metabolic and toxicokinetic studies will be accompanied by experiments to investigate the extent to which intratracheally administered 14C-AFB1 covalently binds to DNA in tissues of the respiratory tract, and to evaluate the effect of AFB1-DNA adduct formation on DNA integrity. These latter studies are considered vital to the project since it is generally postulated that the ability of a compound to covalently bind to and elicit strand breakage, or otherwise modify DNA, is a reasonable indicator of the transforming ability of that compound in the tissue in question.